Varenicline for smoking cessation in schizophrenia: Safety and effectiveness in a 12-week open-label trial

Objective: Varenicline was approved by the FDA in 2006. In 2009, based largely on case reports, the FDA issued a warning of possible adverse neuropsychiatric effects including depression and suicidal thoughts and behavior for varenicline and bupropion. Prospective trials of varenicline have not reported increased incidence of psychiatric adverse events other than sleep disturbance, but smokers with major mental illness have been excluded from large prospective trials of varenicline to date. We sought to evaluate the effect of a standard open-label 12-week varenicline trial on prospectively assessed safety and smoking outcomes in adults with stable, treated schizophrenia spectrum disorder and nicotine dependence. Methods: One-hundred twelve stable outpatients who smoked 10 or more cigarettes/day participated in a 12-week open-label smoking cessation trial of varenicline and weekly group cognitive behavioral therapy. Participants took varenicline for 4 weeks before attempting cessation. Trained raters collected safety and smoking outcome data weekly. Results: Participants demonstrated improved psychotic symptoms, depressive symptoms, and nicotine withdrawal symptoms from baseline to week 12 or early termination. At the end of 12 weeks open-label treatment, the 14- and 28-day continuous abstinence rates were 47.3% and 34%, respectively. Expired carbon monoxide declined significantly during treatment in those who did not achieve abstinence. Conclusions: This prospective study suggests that varenicline may be well tolerated and effective for smoking cessation in combination with group cognitive behavioral therapy in stable outpatients with schizophrenia, a group with high rates of smoking and smoking-attributable morbidity and mortality. This clinical trial is registered at www.clinicaltrials.gov as trial #NCT00621777.